Skip to main content
Erschienen in: Journal of Cancer Survivorship 2/2015

01.06.2015

Predictors of late-onset heart failure in breast cancer patients treated with doxorubicin

verfasst von: Angel Qin, Cheryl L. Thompson, Paula Silverman

Erschienen in: Journal of Cancer Survivorship | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Anthracyclines are an integral component of breast cancer chemotherapy. They exert many cardiotoxic effects, including heart failure. The onset of anthracycline-induced heart failure (AIHF) can occur years after completion of chemotherapy and incurs significant morbidity and mortality. Few studies have attempted to characterize risk factors for its development. Our purpose was to determine the incidence of early and late AIHF in breast cancer survivors and to identify factors that increase the risk for late-onset AIHF.

Methods

Patients with invasive breast cancer who received doxorubicin-containing chemotherapy at University Hospitals Case Medical Center from 1998 to 2006 were included. Medical history and tumor and treatment characteristics were abstracted from medical records. Patients who developed heart failure were compared to those who did not and were also stratified based on timing of heart failure.

Results

One thousand one hundred fifty-three patients received doxorubicin-based chemotherapy for invasive breast cancer with an average follow-up of 7.6 years (standard deviation (SD) = 3.4). The overall incidence of heart failure was 10.4, with a 2.9 and 7.6 % incidence of early- and late-onset heart failure, respectively. Human epidermal growth factor receptor 2 (HER2) status, hypertension, and coronary artery disease were significant predictors for both heart failure groups (p < 0.001). Type II diabetes was a risk factor for the late-onset AIHF group (p < 0.001).

Conclusions

HER2 status and cardiovascular risk factors increased the risk of heart failure among doxorubicin users. Patients with type II diabetes were at increased risk of late-onset AIHF.

Implications for cancer survivors

We identified at risk survivors who may benefit from prolonged monitoring and/or early intervention.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Dang CT. Drug treatments for adjuvant chemotherapy in breast cancer: recent trials and future directions. Expert Rev Anticancer Ther. 2006;6:427–36.CrossRefPubMed Dang CT. Drug treatments for adjuvant chemotherapy in breast cancer: recent trials and future directions. Expert Rev Anticancer Ther. 2006;6:427–36.CrossRefPubMed
2.
Zurück zum Zitat Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, Blum RH. Primary systemic therapy of breast cancer. Oncologist. 2006;11:574–89.CrossRefPubMed Sachelarie I, Grossbard ML, Chadha M, Feldman S, Ghesani M, Blum RH. Primary systemic therapy of breast cancer. Oncologist. 2006;11:574–89.CrossRefPubMed
3.
Zurück zum Zitat Maughan KL, Lutterbie MA, Ham PS. Treatment of breast cancer. Am Fam Physician. 2010;81:1339–46.PubMed Maughan KL, Lutterbie MA, Ham PS. Treatment of breast cancer. Am Fam Physician. 2010;81:1339–46.PubMed
4.
Zurück zum Zitat Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin Pharmacother. 2007;8:1039–58.CrossRefPubMed Barry E, Alvarez JA, Scully RE, Miller TL, Lipshultz SE. Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management. Expert Opin Pharmacother. 2007;8:1039–58.CrossRefPubMed
5.
Zurück zum Zitat Von Hoff DD, Layard MW, Basa P, Davis Jr HL, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–7.CrossRef Von Hoff DD, Layard MW, Basa P, Davis Jr HL, Von Hoff AL, Rozencweig M, et al. Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med. 1979;91:710–7.CrossRef
6.
Zurück zum Zitat Chen MH, Colan SD, Diller L. Cardiovascular disease: cause of morbidity and mortality in adult survivors of childhood cancers. Circ Res. 2011;108:619–28.CrossRefPubMed Chen MH, Colan SD, Diller L. Cardiovascular disease: cause of morbidity and mortality in adult survivors of childhood cancers. Circ Res. 2011;108:619–28.CrossRefPubMed
7.
Zurück zum Zitat Yeh ETH, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53:2231–47.CrossRefPubMed Yeh ETH, Bickford CL. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol. 2009;53:2231–47.CrossRefPubMed
9.
Zurück zum Zitat Sabel MS, Levine EG, Hurd T, Schwartz GN, Zielinski R, Hohn D, et al. Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition. Am J Clin Oncol. 2001;24:425–8.CrossRefPubMed Sabel MS, Levine EG, Hurd T, Schwartz GN, Zielinski R, Hohn D, et al. Is MUGA scan necessary in patients with low-risk breast cancer before doxorubicin-based adjuvant therapy? Multiple gated acquisition. Am J Clin Oncol. 2001;24:425–8.CrossRefPubMed
10.
Zurück zum Zitat Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol. 1998;25:72–85.PubMed Grenier MA, Lipshultz SE. Epidemiology of anthracycline cardiotoxicity in children and adults. Semin Oncol. 1998;25:72–85.PubMed
11.
Zurück zum Zitat Trachtenberg BH, Landy DC, Franco VI, Henkel JM, Pearson EJ, Miller TL, et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol. 2011;32:342–53.CrossRefPubMed Trachtenberg BH, Landy DC, Franco VI, Henkel JM, Pearson EJ, Miller TL, et al. Anthracycline-associated cardiotoxicity in survivors of childhood cancer. Pediatr Cardiol. 2011;32:342–53.CrossRefPubMed
12.
Zurück zum Zitat Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25:3808–15.CrossRefPubMed Pinder MC, Duan Z, Goodwin JS, Hortobagyi GN, Giordano SH. Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol. 2007;25:3808–15.CrossRefPubMed
13.
Zurück zum Zitat Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23:8597–605.CrossRefPubMed Doyle JJ, Neugut AI, Jacobson JS, Grann VR, Hershman DL. Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol. 2005;23:8597–605.CrossRefPubMed
14.
15.
Zurück zum Zitat Brower V. Cardiotoxicity debated for anthracyclines and trastuzumab in breast cancer. J Natl Cancer Inst. 2013;105:835–6.CrossRefPubMed Brower V. Cardiotoxicity debated for anthracyclines and trastuzumab in breast cancer. J Natl Cancer Inst. 2013;105:835–6.CrossRefPubMed
16.
Zurück zum Zitat Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American society of clinical oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991–4008.CrossRefPubMed Carver JR, Shapiro CL, Ng A, Jacobs L, Schwartz C, Virgo KS, et al. American society of clinical oncology clinical evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary late effects. J Clin Oncol. 2007;25:3991–4008.CrossRefPubMed
17.
Zurück zum Zitat Barrett-Lee PJ, Dixon JM, Farrell C, Jones A, Leonard R, Murray N, et al. Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Ann Oncol. 2009;20:816–27.CrossRefPubMed Barrett-Lee PJ, Dixon JM, Farrell C, Jones A, Leonard R, Murray N, et al. Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk. Ann Oncol. 2009;20:816–27.CrossRefPubMed
18.
Zurück zum Zitat Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100:1058–67.CrossRefPubMed Ryberg M, Nielsen D, Cortese G, Nielsen G, Skovsgaard T, Andersen PK. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100:1058–67.CrossRefPubMed
19.
Zurück zum Zitat Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.PubMedCentralCrossRefPubMed Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P, et al. Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337.PubMedCentralCrossRefPubMed
20.
Zurück zum Zitat Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.CrossRefPubMed Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79.CrossRefPubMed
21.
Zurück zum Zitat Feola M, Garrone O, Occelli M, Francini A, Biggi A, Visconti G, et al. Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide. Int J Cardiol. 2011;148:194–8.CrossRefPubMed Feola M, Garrone O, Occelli M, Francini A, Biggi A, Visconti G, et al. Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide. Int J Cardiol. 2011;148:194–8.CrossRefPubMed
22.
Zurück zum Zitat Garrone O, Crosetto N, Lo Nigro C, Catzeddu T, Vivenza D, Monteverde M, et al. Prediction of anthracycline cardiotoxicity after chemotherapy by biomarkers kinetic analysis. Cardiovasc Toxicol. 2012;12:135–42.CrossRefPubMed Garrone O, Crosetto N, Lo Nigro C, Catzeddu T, Vivenza D, Monteverde M, et al. Prediction of anthracycline cardiotoxicity after chemotherapy by biomarkers kinetic analysis. Cardiovasc Toxicol. 2012;12:135–42.CrossRefPubMed
23.
Zurück zum Zitat Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, et al. Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer. 2011;105:1663–8.PubMedCentralCrossRefPubMed Romano S, Fratini S, Ricevuto E, Procaccini V, Stifano G, Mancini M, et al. Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients. Br J Cancer. 2011;105:1663–8.PubMedCentralCrossRefPubMed
24.
Zurück zum Zitat Meinardi MT, Van Der Graaf WTA, Gietema JA, Van Den Berg MP, Sleijfer DT, De Vries EGE, et al. Evaluation of long term cardiotoxicity after epirubicin containing adjuvant chemotherapy and locoregional radiotherapy for breast cancer using various detection techniques. Heart. 2002;88:81–2.PubMedCentralCrossRefPubMed Meinardi MT, Van Der Graaf WTA, Gietema JA, Van Den Berg MP, Sleijfer DT, De Vries EGE, et al. Evaluation of long term cardiotoxicity after epirubicin containing adjuvant chemotherapy and locoregional radiotherapy for breast cancer using various detection techniques. Heart. 2002;88:81–2.PubMedCentralCrossRefPubMed
25.
Zurück zum Zitat Russell SD, Blackwell KL, Lawrence J, Pippen Jr JE, Roe MT, Wood F, et al. Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol. 2010;28:3416–21.CrossRefPubMed Russell SD, Blackwell KL, Lawrence J, Pippen Jr JE, Roe MT, Wood F, et al. Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol. 2010;28:3416–21.CrossRefPubMed
26.
Zurück zum Zitat Verma S, Ewer MS. Is cardiotoxicity being adequately assessed in current trials of cytotoxic and targeted agents in breast cancer? Ann Oncol. 2011;22:1011–8.CrossRefPubMed Verma S, Ewer MS. Is cardiotoxicity being adequately assessed in current trials of cytotoxic and targeted agents in breast cancer? Ann Oncol. 2011;22:1011–8.CrossRefPubMed
27.
Zurück zum Zitat Jannazzo A, Hoffman J, Lutz M. Monitoring of anthracycline-induced cardiotoxicity. Ann Pharmacother. 2008;42:99–104.CrossRefPubMed Jannazzo A, Hoffman J, Lutz M. Monitoring of anthracycline-induced cardiotoxicity. Ann Pharmacother. 2008;42:99–104.CrossRefPubMed
30.
Zurück zum Zitat Allen LA, Yood MU, Wagner EH, Aiello Bowles EJ, Pardee R, Wellman R, et al. Performance of claims-based algorithms for identifying heart failure and cardiomyopathy among patients diagnosed with breast cancer. Med Care. 2012. Allen LA, Yood MU, Wagner EH, Aiello Bowles EJ, Pardee R, Wellman R, et al. Performance of claims-based algorithms for identifying heart failure and cardiomyopathy among patients diagnosed with breast cancer. Med Care. 2012.
31.
Zurück zum Zitat Ryberg M, Nielsen D, Skovsgaard T, Hansen J, Jensen BV, Dombernowsky P. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol. 1998;16:3502–8.PubMed Ryberg M, Nielsen D, Skovsgaard T, Hansen J, Jensen BV, Dombernowsky P. Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breast cancer. J Clin Oncol. 1998;16:3502–8.PubMed
32.
Zurück zum Zitat Romond EH, Jeong J-H, Rastogi P, Swain SM, Geyer CE, Ewer MS, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:3792–9.PubMedCentralCrossRefPubMed Romond EH, Jeong J-H, Rastogi P, Swain SM, Geyer CE, Ewer MS, et al. Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2012;30:3792–9.PubMedCentralCrossRefPubMed
33.
Zurück zum Zitat Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, et al. Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. J. Natl. Cancer Inst. 2014;106. Shelburne N, Adhikari B, Brell J, Davis M, Desvigne-Nickens P, Freedman A, et al. Cancer treatment-related cardiotoxicity: current state of knowledge and future research priorities. J. Natl. Cancer Inst. 2014;106.
34.
Zurück zum Zitat Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.PubMedCentralCrossRefPubMed Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365:1273–83.PubMedCentralCrossRefPubMed
35.
Zurück zum Zitat Sysa-Shah P, Xu Y, Guo X, Belmonte F, Kang B, Bedja D, et al. Cardiac-specific over-expression of epidermal growth factor receptor 2 (ErbB2) induces pro-survival pathways and hypertrophic cardiomyopathy in mice. PLoS One. 2012;7:e42805.PubMedCentralCrossRefPubMed Sysa-Shah P, Xu Y, Guo X, Belmonte F, Kang B, Bedja D, et al. Cardiac-specific over-expression of epidermal growth factor receptor 2 (ErbB2) induces pro-survival pathways and hypertrophic cardiomyopathy in mice. PLoS One. 2012;7:e42805.PubMedCentralCrossRefPubMed
36.
Zurück zum Zitat Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetol. 2014. Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetol. 2014.
37.
Zurück zum Zitat Huynh K, Bernardo BC, McMullen JR, Ritchie RH. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther 2014. Huynh K, Bernardo BC, McMullen JR, Ritchie RH. Diabetic cardiomyopathy: mechanisms and new treatment strategies targeting antioxidant signaling pathways. Pharmacol Ther 2014.
38.
Zurück zum Zitat Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, et al. Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci. 2003;105:591–9.CrossRefPubMed Vinereanu D, Nicolaides E, Tweddel AC, Mädler CF, Holst B, Boden LE, et al. Subclinical left ventricular dysfunction in asymptomatic patients with type II diabetes mellitus, related to serum lipids and glycated haemoglobin. Clin Sci. 2003;105:591–9.CrossRefPubMed
39.
Zurück zum Zitat Ky B, Vejpongsa P, Yeh ETH, Force T, Moslehi JJ. Emerging paradigms in cardiomyopathies associated with cancer therapies. Circ Res. 2013;113:754–64.PubMedCentralCrossRefPubMed Ky B, Vejpongsa P, Yeh ETH, Force T, Moslehi JJ. Emerging paradigms in cardiomyopathies associated with cancer therapies. Circ Res. 2013;113:754–64.PubMedCentralCrossRefPubMed
40.
Zurück zum Zitat Poterucha JT, Kutty S, Lindquist RK, Li L, Eidem BW. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr. 2012;25:733–40.CrossRefPubMed Poterucha JT, Kutty S, Lindquist RK, Li L, Eidem BW. Changes in left ventricular longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent decreased left ventricular ejection fraction. J Am Soc Echocardiogr. 2012;25:733–40.CrossRefPubMed
41.
Zurück zum Zitat Stoodley PW, Richards DAB, Hui R, Boyd A, Harnett PR, Meikle SR, et al. Two-dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr. 2011;12:945–52.CrossRefPubMed Stoodley PW, Richards DAB, Hui R, Boyd A, Harnett PR, Meikle SR, et al. Two-dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy. Eur J Echocardiogr. 2011;12:945–52.CrossRefPubMed
Metadaten
Titel
Predictors of late-onset heart failure in breast cancer patients treated with doxorubicin
verfasst von
Angel Qin
Cheryl L. Thompson
Paula Silverman
Publikationsdatum
01.06.2015
Verlag
Springer US
Erschienen in
Journal of Cancer Survivorship / Ausgabe 2/2015
Print ISSN: 1932-2259
Elektronische ISSN: 1932-2267
DOI
https://doi.org/10.1007/s11764-014-0408-9

Weitere Artikel der Ausgabe 2/2015

Journal of Cancer Survivorship 2/2015 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.